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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2021

01-12-2021 | Shock | Research

The EGFR-HSF1 axis accelerates the tumorigenesis of pancreatic cancer

Authors: Weikun Qian, Ke Chen, Tao Qin, Ying Xiao, Jie Li, Yangyang Yue, Cancan Zhou, Jiguang Ma, Wanxing Duan, Jianjun Lei, Liang Han, Li Li, Xin Shen, Zheng Wu, Qingyong Ma, Zheng Wang

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2021

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Abstract

Background

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant diseases because of its non-symptomatic tumorigenesis. We previous found heat shock factor 1 (HSF1) was critical for PDAC progression and the aim of this study was to clarified the mechanisms on early activation of HSF1 and its role in the pancreatic cancer tumorigenesis.

Methods

The expression and location of HSF1 on human or mice pancreatic tissues were examined by immunohistochemically staining. We mainly used pancreatic acinar cell 3-dimensional (3D) culture and a spontaneous pancreatic precancerous lesion mouse model called LSL-KrasG12D/+; Pdx1-Cre (KC) (and pancreatitis models derived from KC mice) to explore the pro-tumorigenesis mechanisms of the HSF1 in vitro and in vivo. Bioinformatics and molecular experiments were used to explore the underlying mechanisms between HSF1 and epidermal growth factor receptor (EGFR).

Results

In this study, we found that pharmacological inhibition of HSF1 slowed pancreatic cancer initiation and suppressed the pancreatitis-induced formation of pancreatic precancerous lesion. Next, bioinformatics analysis revealed the closely linked between HSF1 and EGFR pathway and we also confirmed their parallel activation in pancreatic precancerous lesions. Besides, the pharmacological inhibition of EGFR suppressed the initiation of pancreatic cancer and the activation of HSF1 in vivo. Indeed, we demonstrated that the EGFR activation that mediated pancreatic cancer tumorigenesis was partly HSF1-dependent in vitro.

Conclusion

Hence, we concluded that the EGFR-HSF1 axis promoted the initiation of pancreatic cancer.
Appendix
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Metadata
Title
The EGFR-HSF1 axis accelerates the tumorigenesis of pancreatic cancer
Authors
Weikun Qian
Ke Chen
Tao Qin
Ying Xiao
Jie Li
Yangyang Yue
Cancan Zhou
Jiguang Ma
Wanxing Duan
Jianjun Lei
Liang Han
Li Li
Xin Shen
Zheng Wu
Qingyong Ma
Zheng Wang
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2021
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-020-01823-4

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